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D Darmon

Publications and source records attributed to D Darmon.

12 recordsLinked to original sources
PubMed2001

Transient urethral obstruction predisposes to ascending pyelonephritis and tubulo-interstitial disease: studies in rats.

Chronic tubulo-interstitial disease, an important cause of end-stage renal disease, often results from the combined effects of a disturbed urinary outflow tract and urinary tract infection. Acute unilateral ureteral obstruction in rats rapidly induces foci of medullary necrosis, confined to the region of the papilla and fornices. This injury may provide a nidus for bacterial invasion and may invoke reactive and regenerative changes, ultimately leading to chronic pyelonephritis and tubulo-interstitial nephropathy. To explore this possibility, adult rats underwent renal morphological evaluation 2-7 days following transient 24-h unilateral ureteral obstruction. In some experiments the bladder was inoculated with bacteria (10(8)-10(9) cfu/ml Escherichia coli in 0.5 ml) after release of ureteral obstruction, with subsequent cultures obtained from the pelvis of both kidneys and from the urinary bladder. Morphologic evaluation of perfusion-fixed kidneys, 2-7 days after the release of 24-h ureteral obstruction disclosed papillary necrosis, urothelial proliferation, marked inner-stripe interstitial expansion, and fibrosis and proximal tubular (S3) dilatation. The lateral (perihilar region) was predominantly affected, with lesions spreading from the fornices. There was some progression of interstitial fibrosis during the postobstructive time course or following more prolonged ureteral obstruction. By contrast, infection hardly contributed to the tubulointerstitial changes. In rats subjected to infection, cultures were positive in all 15 postobstructive kidneys, as opposed to five contralateral kidneys (P < 0.0001). Viable counts from the postobstructive kidney were also higher than those from the contralateral side (79,000 +/- 12,000 vs 2900 +/- 1600 cfu/ml, mean +/- SEM, P < 0.0001), and were comparable to those obtained from the bladder (77,000 +/- 13,000 cfu/ml). We conclude that transient ureteral obstruction predisposes to ascending pyelonephritis and to tubulointerstitial disease. This vulnerability may relate to altered urodynamics and medullary tissue destruction.

Animals↗
PubMed2001

Kidney involvement and renal manifestations in non-Hodgkin's lymphoma and lymphocytic leukemia: a retrospective study in 700 patients.

Renal involvement as part of systemic lymphoma (LY) is quite frequent, however, primary extranodal renal non-Hodgkin's lymphoma (NHL) is extremely rare, and only about 65 cases have been reported in the world literature. In a retrospective study of renal manifestations in 700 patients with documented LY and chronic lymphocytic leukemia (CLL) seen at our hospital during 1986-95, 83 patients had signs of acute renal failure. Only five of these had proven renal infiltration, but none of them satisfied the criteria for primary renal LY. Glomerulonephritis (GN) has also rarely been reported in association with LY and CLL, and only 37 glomerular lesions in NHL and 42 in CLL have been documented, respectively. GN may precede, coexist, or follow the diagnosis of LY by several years. Of the 42 cases of CLL reported worldwide, 36 had nephrotic syndrome. Renal failure was seen in about one third. The most common glomerular lesion reported is membranoproliferative GN, followed by membranous GN. In our study, we found only five biopsy-proven cases with GN amongst the 700 patients seen. In this report we also briefly describe some rare interesting associated renal syndromes in CLL and NHL.

Acute Kidney Injury↗
PubMed2001

Immunotactoid glomerulopathy with massive bone marrow deposits in a patient with IgM kappa monoclonal gammopathy and hypocomplementemia.

A case of immunotactoid glomerulopathy with an amyloid-like material in the glomeruli and bone marrow is described. Clinically the patient was diagnosed as having severe nephrotic syndrome, hypocomplementemia, and IgM kappa monoclonal gammopathy. Immunotactoid glomerulopathy is an unusual cause of glomerulonephritis, characterized by Congo red-negative, amyloid-like deposits in the glomeruli. This unusual case presentation shows that immunotactoid glomerulopathy may be a manifestation of systemic disease. This patient also presented with hypocomplementemia, an extremely rare associated finding that has been reported previously in only four cases of immunotactoid glomerulopathy.

Aged↗
PubMed1999

Tissue oxygenation modifies nitric oxide bioavailability.

OBJECTIVE: Because changes in blood oxygenation acutely alter vascular tone, we explored a possible modulation of nitric oxide-induced vasodilation (nitrovasodilation) by oxygen. METHODS: We studied the effects of manipulation of tissue oxygenation on renal parenchymal nitric oxide (NO) with a selective NO electrode placed in the well-oxygenated renal cortex or in the physiologically hypoxemic outer medulla. RESULTS: In the cortex, as expected, NO signals fell in response to the NO synthase (NOS) inhibitor L-NAME. By contrast, in the outer medulla, NO signals paradoxically rose following NOS inhibition, known to intensify local hypoxia. Other manipulations that intensify outer medullary hypoxia (such as indomethacin or radiologic contrast media) increased local NO readings, while measures known to ameliorate outer medullary hypoxia (furosemide, L-arginine, hypotension) reduced regional NO readings. CONCLUSIONS: Oxygen appears to modulate NO bioavailability, in particular, in tissues with low ambient pO2, perhaps through enhanced binding to oxygenated hemoglobin. It is proposed that this phenomenon may participate in physiological microvascular regulation, with hypoxemia enhancing NO concentration, while hyperoxemia resulting in accelerated NO removal.

Animals↗
PubMed1997

Antiproliferative activity to glomerular mesangial cells and receptor binding of a heparin-mimicking polyaromatic anionic compound.

Proliferation of mesangial cells (MC) is a key feature in the pathogenesis of numerous renal diseases involving the glomerulus. Heparin, one of several compounds capable of suppressing MC proliferation, did not prove beneficial in the treatment of human glomerular diseases. In a search for a superior antiproliferative agent, a synthetic polyaromatic "heparin mimicking" compound (RG-13577, polymer of 4-hydroxyphenoxy acetic acid, M(r) approximately 5800), previously reported to inhibit the proliferation of vascular smooth muscle cells, was applied. RG-13577 exhibits approximately 1% of the anticoagulant activity of heparin and is nontoxic in animal experiments. Proliferation of primary rat MC was almost completely inhibited in the presence of 10 to 25 micrograms/ml RG-13577, and 50% inhibition was obtained at 1 to 5 micrograms/ml RG-13577. The cells resumed their normal growth rate after removal of RG-13577 from the culture medium. Under the same conditions, heparin exerted only a small inhibitors effect. RG-13577 inhibited signaling (i.e., tyrosine phosphorylation) and MC proliferation induced by both basic fibroblast growth factor and platelet-derived growth factor. RG-13577 binds to a naturally produced extracellular matrix, and the bound molecule retained its antiproliferative effect toward MC. 14C-Labeled RG-13577 also binds to cultured MC in a specific and saturable manner. Binding of 14C-RG-13577 was reduced by 80 to 90% in the presence of excess unlabeled RG-13577, apolipoprotein E, or lactoferrin, but there was no effect with heparin. Furthermore, the antiproliferative effect of RG-13577 was abolished in the presence of lactoferrin. It is proposed that compound RG-13577 inhibits MC proliferation through neutralization of growth-promoting factors, primarily heparin-binding growth factors, and possibly through binding to specific cell surface receptors, most likely the LDL receptor-related protein. RG-13577 and related polyanionic compounds may be applied to inhibit MC proliferation in glomerular diseases.

Animals↗
PubMed1989

The in vivo and in vitro effect of calmodulin antagonists on the renal actions of 25(OH) vitamin D3 in the rat.

Previous work from this laboratory has demonstrated that 25(OH) vitamin D3 [25(OH)D3] acutely suppresses the phosphaturic action of parathyroid hormone (PTH) and interferes with the PTH-induced activation of adenylate cyclase (AC). Calmodulin inhibitors block vitamin D-induced Ca2+ transport in the gut and phosphorus uptake in renal BBMV's. We have examined whether calmodulin antagonists affect the renal action of 25(OH)D3. Acute clearance experiments were performed in PTH-infused parathyroidectomized rats receiving 25(OH)D3 after pretreatment with trifluoperazine (TFP) or promethazine (P). In vitro PTH-induced activation of renal AC was also studied in membrane preparations from pretreated rats in the presence of 25(OH)D3. 25(OH)D3 reduced the PTH-stimulated increase in fractional excretion of phosphorus (CP/CIn) from 0.292 +/- 0.024 to 0.195 +/- 0.018 (p less than 0.005) and urinary cAMP from 149.3 +/- 20.3 to 78.1 +/- 10.4 pmol/min (p less than 0.01) and also blunted AC activation in vitro. TFP but not P abolished the effects of 25(OH)D3 both in vivo and in vitro. R 24571 also abolished the in vitro effect of 25(OH)D3. Thus, (1) TFP abolishes both the antiphosphaturic and the AC/cAMP-related actions of 25(OH)D3, (2) P does not have these effects, and (3) R 24571 abolishes the in vitro effect of 25(OH)D3. These results suggest that the antiphosphaturic effect of 25(OH)D3 acting via the AC/cAMP system may be calmodulin dependent.

Adenylyl Cyclases↗
PubMed1989

Oncogenous osteomalacia: a case study.

A case of oncogenous osteomalacia due to a fibrosarcoma of the maxilla is reported, with a 19 year course before treatment. Metabolic studies of calcium and phosphorus were performed 3 and 19 years after the first symptomology. There was a negative balance for both phosphorus and calcium with low serum levels of 1,25-dihydroxyvitamin D which were corrected by resection of the tumor. Portions of the tumor were cultured and the supernatant did not affect phosphorus transport by a proximal tubule kidney cell line. Other portions were injected into athymic nude mice where they resulted in hypophosphatemia and phosphaturia, thus confirming the endocrine nature of the oncogenous osteomalacia factor.

Adult↗
PubMed1984

[Should closed-heart mitral commissurotomies still be performed? Apropos of 168 operations, 108 open-heart and 60 closed-heart].

Mitral commissurotomy is known to give good results but the best surgical technique (open heart or closed heart) remains uncertain. Results of open heart commissurotomy (OC), 108 patients (Group I) and closed heart commissurotomy (CC), 60 patients (Group II) were compared. The population comprised 81% females and the average age was 39 +/- 12 years. Only cases of pure or very predominant mitral stenosis (MS) were included. The preoperative state of the patients in Group I was poorer than the one in Group II (repeat commissurotomy 8.3% compared to 1.7%, p less than 0.04; associated mitral regurgitation 41% compared to 27%, p less than 0.04; cardiothoracic ratio 0.54 +/- 0.07 compared to 0.51 +/- 0.06, p less than 0.01). A more complete surgical cure was possible in Group I. Both commissures were liberated in 99% of OC compared to 25% CC (p less than 0.001). Mitral valvuloplasty was associated in 87% of OC (63 cases on the papillary muscles, 21 cases on the chordae tendinae and 60 cases on the mitral annulus). Operative mortality was low and did not differ significantly between the two groups (zero in CC; 1.8% in OC). Overall survival rates were excellent (95% 5 year survival, 85% 7 year survival). The reoperation rate at 5 years was 7.4% and at 7 years, 23.9%, and did not differ with the surgical technique used. The functional result was good (patients in Class I or II of the NYHA classification 84% at 5 years; 75% at 7 years; identical for both groups). Significant late valvular "dysfunction" was rare after OC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Endotoxin-induced renal failure. I. A role for altered renal microcirculation.

The pathogenesis of sepsis-induced renal failure is multifactorial and only partially understood. In these studies we evaluated intrarenal microcirculatory changes during endotoxemia and the potential role of nitric oxide (NO) and endothelin in these changes. In anesthetized rats endotoxin infusion [lipopolysaccharide (LPS), Escherichia coli serotype 0127:B8; 10 mg/kg/h] resulted in hypotension and a transient enhancement of renal blood flow, with cortical vasodilation and a loss of outer medullary vasodilatory response to hypotension. The initial cortical vasodilation was abolished by the NO synthase inhibitor NG-nitro-L-arginine methyl ester, but not by indomethacin. Direct NO measurements disclosed a gradual rise in cortical NO, despite the waning vasodilatory effect, suggesting antagonizing vasoconstrictive stimuli. In rats pretreated by LPS (1 mg/kg i.p. 1 day earlier) the renal blood flow was reduced to 55% of that of controls. Moreover, the vasodilatory response to LPS infusion was converted into profound cortical and medullary vasoconstriction. In these preconditioned rats the endothelin receptor antagonist bosentan evoked a vasodilatory response and attenuated the vasoconstrictive reaction to LPS infusion. The infusion of another LPS (E. coli serotype 0111:B4) exerted predominant and protracted renal vasodilation without hypotension. In conclusion, different LPS exert diverse systemic and renal hemodynamic responses. The 0127:B8 serotype attenuates renal medullary vasodilation during hypotension, exerts transient cortical vasodilation, and following repeated exposure induces profound renal vasoconstriction. NO and endothelin participate in LPS-induced vascular responses that may predispose to hypoxic tubular damage.

Animals↗
PubMedDate not supplied

Endotoxin-induced renal failure. II. A role for tubular hypoxic damage.

Endotoxin-induced hypotension and altered renal microcirculation could lead to tubular injury, particularly at the physiologically hypoxic outer medulla. We explored this hypothesis in isolated perfused kidneys and in vivo in rats subjected to endotoxemia. Rat kidneys were removed 15 min after endotoxin injection in vivo (from Escherichia coli 0127:B8, 1 mg/kg i.p.) and perfused with oxygenated medium supplemented with 20 amino acids and endotoxin. Glomerular filtration rate and filtration fraction markedly declined (0.4 +/- 0. 1 ml/min and 1.1 +/- 0.1, respectively) as compared with control kidneys (0.7 +/- 0.1 ml/min and 1.8 +/- 0.1, n = 8-12 per group; p < 0.05). Hypoxic injury to medullary thick ascending limbs in the innermost outer medulla increased (47 +/- 9% of tubules vs. 16 +/- 8% in controls, p < 0.05). When rats were preconditioned with an additional endotoxin injection 16 h earlier (a manipulation that markedly reduces cortical and medullary blood flow), glomerular filtration rate and filtration fraction further declined to 0.1 +/- 0.0 ml/min and 0.4 +/- 0.1, respectively (p < 0.01), and tubular sodium reabsorption fell to 81 +/- 12 vs 98 +/- 0% in controls (p < 0.05). Tubular damage, however, did not increase (20 +/- 7%), probably reflecting a decline in reabsorptive workload and oxygen requirement. In rats subjected to a single or two repeated daily doses of endotoxin (1 mg/kg i.p.) plasma creatinine comparably rose 41% on the average over 24 h, creatinine clearance fell by 27% (p < 0.0001), but tubular damage was absent. By contrast, in rats preconditioned with indomethacin and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (10 mg/kg), the addition of endotoxin markedly augmented outer medullary hypoxic tubular damage both in S(3) segments (27 +/- 10 vs 1 +/- 1%) and in medullary thick ascending limbs (38 +/- 11 vs. 10 +/- 5%, n = 7-8; p < 0.05). It is concluded that under special conditions, such as altered medullary oxygen balance or defective nitric oxide or prostaglandin synthesis, endotoxin may predispose to hypoxic outer medullary tubular damage.

Absorption↗